Anti-NTM monoclonal antibody Made to order

Objective: The international outbreak of cardiac-surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCDs). In general, non-tuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than 4 years. Methods: Five LivaNova 3T (London, UK) HCDs, acquired factory-new in 2014, were followed prospectively. Until mid-April 2014, the HCDs were maintained according to the manufacturer's recommendations, and subsequently, they were maintained according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. Results: Of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were M. chimaera [N=120 (67.4%)], Mycobacterium gordonae [N=35 (19.7 %)] and Mycobacterium paragordonae [N=17 (9.6%)]. Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient circuit than the cardioplegia circuit of the HCD. Three (2.0%) of 150 air samples grew NTM. Conclusion: Growth of NTM in HCD water samples was common. Diverse NTM species were detected, with M. chimaera being the most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on an HCD-associated outbreak with Mycobacterium abscessus confirmed a potential threat. (C) 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Botulinum neurotoxins (BoNT) are potential biothreat agents due to their high lethality, potency, and ease of distribution, thus the development of antitoxins is a high priority to the US government. This study examined pre-clinical pharmacokinetic studies in rats of four oligoclonal anti-BoNT mAb-based therapeutics (NTM-1631, NTM-1632, NTM-1633, NTM-1634) for five BoNT serotypes (A, B, E, C, and D). NTM-1631, NTM-1632, and NTM-1633 each consist of three IgG1 mAbs, each with a distinct human or humanized variable region which bind to distinct epitopes on BoNT serotype A, B, or E respectively. NTM-1634 consists of four human immunoglobulin G1 (IgG1) mAbs binding BoNT C/D mosaic toxins. The mechanism of these antitoxins requires that three antibodies simultaneously bind toxin to achieve rapid clearance. Rats (total 378) displayed no adverse clinical signs attributed to antibody treatment from any of the antitoxins. Pharmacokinetic evaluation demonstrated that the individual mAbs are slowly eliminated, exhibiting dose-dependent exposure and long elimination half-lives ranging from 6.5 days to 10 days. There were no consistent differences observed between males and females or among the individual antibodies in each formulation in half-life. Anti-drug antibodies (ADA) were observed, as expected for human antibodies administered to rats. The results presented were used to support the clinical investigation of antibody-based botulism antitoxins.